Respiratory infection of neonatal mice with an aerosol of Bordetella pertussis provides a reproducible system for the study of the host-pathogen interactions involved in respiratory infection and subsequent disease. Analysis of genetic mutants of Bordetella pertussis in this model is a powerful tool that allows us to identify new virulence determinants. Following infection with wild-type B. pertussis 18323, B. pertussis grows in the lungs of infected mice, concomitant with an increase in peripheral leukocyte count and decrease in weight, followed by death. We have previously identified a new virulence associated factor, activated by the vir locus in this model. A second class of transposon insertion mutants, whose expression is repressed by the vir locus, was analyzed in the mouse aerosol model. One of these mutants was determined to be defective in respiratory tract persistence, lymphocytosis, and the ability to kill, while a second vir repressed mutant remained as virulent as wild-type B. pertussis 18323. The role of these vir repressed genes in pathogenesis, remains to be elucidated.